Belzutifan Approved for Advanced Renal Cell Carcinoma

The US Food and Drug Administration (FDA) has approved belzutifan (Welireg) for adults with advanced renal cell carcinoma following progression on a PD-1/L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

The approval makes belzutifan the first agent indicated for renal cell carcinoma that has progressed after checkpoint inhibition and a VEGF-TKI.

The oral hypoxia-inducible factor (HIF)-2 alpha inhibitor was previously approved in 2021 for von Hippel-Lindau syndrome–associated renal cell carcinoma, central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors not requiring immediate surgery.

Approval for the new indication was based on results of the LITESPARK-005 trial, which randomly assigned 746 patients with unresectable, locally advanced, or metastatic clear cell renal cell carcinoma to either belzutifan (120 mg) or the MTOR inhibitor everolimus (10 mg) orally once a day.

Median progression-free survival was 5.6 months for both drugs, but belzutifan reduced the risk for progression or death by 25% (hazard ratio, 0.75), according to Merck, the manufacturer of the drug.

The objective response rate for belzutifan was 22%, with a complete response in 3% of study participants and a partial response in 19%. For everolimus, the objective response rate was 4%, all partial responses.

Serious adverse events occurred in 38% of patients taking belzutifan, including hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Overall, 6% of patients discontinued treatment due to adverse events, which were fatal in 3.2% of participants. Labeling carries a boxed warning of teratogenicity.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected].